Journal of Ethnopharmacology 122 (2009) 430–433

Contents lists available at ScienceDirect

Journal of Ethnopharmacology
journal homepage: www.elsevier.com/locate/jethpharm

Screening of the topical anti-inflammatory activity of the bark of Acacia cornigera

Willdenow, Byrsonima crassifolia Kunth, Sweetia panamensis Yakovlev and the
leaves of Sphagneticola trilobata Hitchcock
M. Maldini a , S. Sosa b , P. Montoro a , A. Giangaspero b , M.J. Balick c , C. Pizza a,∗ , R. Della Loggia b
a
Department of Pharmaceutical Science, University of Salerno, via Ponte don Melillo, 84084, Fisciano (Sa), Italy
b
Department of Materials and Natural Resources, University of Trieste, Via A. Valerio 6, 34127 Trieste, Italy
c
Institute of Economic Botany, The New York Botanical Garden, Bronx, NY 10458-5126, USA

a r t i c l e i n f o a b s t r a c t

Article history: Ethnopharmacological relevance: An investigation of topical anti-inflammatory activity was undertaken
Received 28 November 2008 on plants used in Central America traditional medicine.
Received in revised form 27 January 2009 Aim of study: Four herbal drugs used in the folk medicine of Central America to treat inflammatory skin
Accepted 2 February 2009
affections (Acacia cornigera bark, Byrsonima crassifolia bark, Sphagneticola trilobata leaves and Sweetia
Available online 11 February 2009
panamensis bark) were evaluated for their topical anti-inflammatory activity.
Materials and methods: Petroleum ether, chloroform and methanol extracts were obtained for herbal
Keywords:
medicines and then extracts were tested on Croton oil-induced ear dermatitis model in mice.
Sweetia panamensis
Byrsonima crassifolia
Results: Almost all the extracts reduced the Croton oil-induced ear dermatitis in mice and the chloroform
Acacia cornigera ones showed the highest activity, with ID50 (dose giving 50% oedema inhibition) values ranging from
Sphagneticola trilobata 112 ␮g/cm2 (Byrsonima crassifolia) to 183 ␮g/cm2 (Sphagneticola trilobata). As reference, ID50 of the non-
Anti-inflammatory activity steroidal anti-inflammatory drug indomethacin was 93 ␮g/cm2 .
Conclusions: Lipophilic extracts from these species can be regarded as potential sources of anti-
inflammatory principles.
© 2009 Elsevier Ireland Ltd. All rights reserved.

1. Introduction conditions, representing potential source of anti-inflammatory

Inflammation is a complex biological response of vascular tis-
sues to harmful stimuli, such as pathogens, damaged cells, or
irritants. It is a defence mechanism aimed to remove the injurious
stimuli and initiate the tissue healing process. Anyway, inflamed tis-
sues can respond to noxious stimuli producing different bioactive
mediators which interact with many cell types and molecules to
amplify the phlogistic reaction. This event can lead to uncontrolled
inflammatory response that may cause or sustain a pathologic pro-
cess involved in different pathologies. Inflammation is treated with
steroidal and non-steroidal anti-inflammatory drugs, known for
their efficacy but also for a number of undesirable side effects
(Saklatvala, 2002; O’connor et al., 2003; Davies et al., 2006; Schoepe
et al., 2006). Thus, new effective and safe anti-inflammatory agents
are needed.
It has been widely shown that herbal drugs are used, in tradi-
tional medicine of many countries, to cure various inflammatory
∗ Corresponding author. Tel.: +39 089 969765; fax: +39 089 969602.
E-mail address: pizza@unisa.it (C. Pizza).
agents. Nevertheless, though their use is supported by an old tra-
dition among native peoples, scientific studies demonstrating the
real pharmacological properties of these plants are often lacking.
Therefore, scientific studies are required to judge the real efficacy
of the medicinal properties popularly claimed for some plants.
This study is aimed to evaluate the topical anti-inflammatory
properties of four medicinal plants, used in the traditional medicine
of Central America to prepare decoctions, infusions or baths as
remedies against inflammatory-based disorders: Sweetia pana-
mensis (Bentham) Yakovlev (Fabaceae) bark, Byrsonima crassifolia
(L.) Kunth (Malpighiaceae) bark, Acacia cornigera (L.) Willdenow
(Mimosaceae) bark and Sphagneticola trilobata (L.) Pruski [=Wedelia
trilobata (L.) Hitchcock; Asteraceae] leaves.
Sphagneticola trilobata is a weed employed to treat back-
ache, muscle cramps, rheumatism, stubborn wounds, sores and
swellings, and arthritic painful joints (Arvigo and Balik, 1993). A
study on the biological properties of Sphagneticola trilobata demon-
strated its antimicrobial properties for the n-hexane and ethyl
acetate extracts of the aerial parts without flowers against Gram-
positive and/or Gram-negative bacteria, but not against yeasts and
fungi (Taddei and Rosas-Romero, 1999). The bark and thorns of Aca-
cia cornigera are used as snakebite remedy and to treat onset of

0378-8741/$ – see front matter © 2009 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.jep.2009.02.002
 M. Maldini et al. / Journal of Ethnopharmacology 122 (2009) 430–433
asthma attacks, cough, lung congestion and headaches (Arvigo and
Balik, 1993), while antibacterial properties were reported by Bork et
al. (1996). Byrsonima crassifolia is a small evergreen tree and its bark
is employed in folk medicine to treat coughs, gastrointestinal dis-
orders, gynaecological inflammations, skin infections (Heinrich et
al., 1992; Leonti et al., 2001) and snakebites (Rastrelli et al., 1997).
Experimental studies on this species showed antioxidant proper-
ties for its bark and leaves hydroalcoholic extracts (Silva et al.,
2007), spasmogenic effects (Bejar and Malone, 1993; Bejar et al.,
1995), antimicrobial activity for roots and stems organic extracts
(Caceres et al., 1990, 1991; Martinez-Vasquez et al., 1999), antipro-
tozoarial activities for bark and leaves alcohol extracts (Berger et
al., 1998; Peraza-Sánchez et al., 2007), and central nervous system
depressant activity for leaves and bark aqueous extracts (Morales
et al., 2001). Sweetia panamensis bark infusions are traditionally
employed for the treatment of stomach pain, respiratory prob-
lems, diarrhoea and malaria (Andrade-Cetto and Heinrich, 2005).
Furthermore, a hypoglycaemic effect of Sweetia panamensis bark
extracts was observed on streptozotocin-induced diabetes in rats
(Andrade-Cetto and Wiedenfeld, 2004).
In order to evaluate the topical anti-inflammatory activity, the
plant material from each species was extracted by solvents of
increasing polarity grade (petroleum ether, chloroform, methanol)
and the obtained extracts were evaluated for their ability to inhibit
the Croton oil-induced ear dermatitis in mice (Tubaro et al., 1985).
As reference, the non-steroidal anti-inflammatory drug (NSAID)
indomethacin was used.
2. Materials and methods
2.1. Plant materials
Plant materials were collected in Belize (Central America) in
February 1999 and authenticated by Professor M.J. Balick. Voucher
specimens (Acacia cornigera n.34, Byrsonima crassifolia n.26, Sphag-
neticola trilobata n.38 and Sweetia panamensis n.18) were dried and
deposited at the New York Botanical Garden (NY, USA).
2.2. Chemicals
Croton oil and indomethacin were purchased from Sigma Chem-
ical Co. (St. Louis, MO, USA) and ketamine hydrochloride from
Virbac (Milan, Italy). Other reagents and solvents used for the
extractions, of analytical grade, were purchased from Carlo Erba
(Rodano, Italy).
2.3. Extraction
The air-dried and powdered plant materials (160.03 g of Aca-
cia cornigera bark, 226.06 g of Sweetia panamensis bark, 42.01 g of
Sphagneticola trilobata leaves, 174.52 g of Byrsonima crassifolia bark)
were sequentially extracted, two times for three days, with 1 l of
petroleum ether, chloroform and methanol, at room temperature.
The solvents were removed from the filtered extract solutions under
vacuum at 30 ◦ C in a rotary evaporator, until dry petroleum ether,
chloroform and methanol extracts were obtained. Final yields of
extractions (w/w) were: 0.27% petroleum ether extract, 1.2% chlo-
roform extract and 4.1% methanol extract for Acacia cornigera, 0.89%,
0.45% and 18.67% for Sweetia panamensis, 0.55%, 0.95% and 11.6% for
Sphagneticola trilobata and 1.28%, 0.27% and 12.65% for Byrsonima
crassifolia, respectively.
2.4. Topical anti-inflammatory activity
Animal experiments complied with the Italian D.L. n. 116 of
27 January 1992 and associated guidelines in the European Com-
431
munities Council Directive of 24 November 1986 (86/609 ECC),
concerning animal welfare. Topical anti-inflammatory activity was
evaluated as inhibition of the Croton oil-induced ear dermatitis
in mice (Tubaro et al., 1985). Male CD-1 mice (28–32 g; Harlan
Italy, S. Pietro al Natisone, Italy) were anaesthetised with ketamine
hydrochloride (145 mg/kg, intraperitoneally) prior to induce the ear
dermatitis. Skin inflammation was induced by applying 80 ␮g of
Croton oil dissolved in 15 ␮l of acetone (for petroleum ether and
chloroform extracts, and the relevant controls) or suspended in
the same volume of 42% aqueous ethanol (v/v) (methanol extracts,
and the relevant controls) to the inner surface of the right ear of
mice (surface: about 1 cm2 ). The left ear remained untreated. The
substances under testing were applied together with the Croton
oil, except for control animals which received only the irritant. Six
hours later, mice were sacrificed and a plug (Ø 6 mm ) was removed
from both the treated and the untreated ears. Inflammation was
measured quantifying the oedematous response by the weight dif-
ference between the two plugs. The anti-inflammatory activity was
expressed as percentage of oedema reduction in treated mice with
regard to control mice. Two experimental groups of five animals
were tested for each dose level.
2.5. Statistical analysis
Oedema was expressed as mean ± standard error of the mean.
Data were analyzed by one-way analysis of variance followed by
the Dunnett’s test for multiple comparisons of unpaired data, and
a probability level lower than 0.05 was considered as significant.
ID50 values (dose giving 50% oedema inhibition) were calculated
by graphic interpolation of the dose–effect curves.
3. Results
Preliminary screening of the topical anti-inflammatory activ-
ity at the dose of 300 ␮g/cm2 showed that almost all the extracts
reduced the oedematous response to certain extent. In particu-
lar, except Sphagneticola trilobata methanol extract, all the extracts
provoked a significant oedema reduction which ranged from 16%
(Acacia cornigera bark methanol extract) to 71% (Acacia cornig-
era bark and Byrsonima crassifolia bark chloroform extracts). The
chloroform extracts were the most active, reducing the oedema-
tous response by about 70%, followed by petroleum ether extracts
which induced oedema reductions ranging from 38% (Acacia cornig-
era bark) to 58% (Byrsonima crassifolia bark), and by methanol
extracts which determined less than 20% oedema reduction. As
reference, the non-steroidal anti-inflammatory drug indomethacin
(100 ␮g/cm2 ) reduced the oedematous response by 60% (Table 1).
The dose–effect relationship of the most active extracts,
the chloroform ones, was evaluated in comparison to that of
the reference drug indomethacin. At doses ranging from 30 to
300 ␮g/cm2 , each chloroform extract provoked a dose-dependent
oedema reduction. The relationship between the administered
doses and the observed effects allowed an estimation of their
anti-inflammatory potency by calculating the ID50 values (dose giv-
ing 50% oedema inhibition). The most active chloroform extracts
were obtained from Byrsonima crassifolia and Acacia cornigera barks
(ID50 = 112 and 116 ␮g/cm2 , respectively), which anti-inflammatory
potency was comparable to that of the NSAID indomethacin
(ID50 = 93 ␮g/cm2 ). Also the extracts of Sweetia panamensis bark and
Sphagneticola trilobata leaves (ID50 = 180 and 183 ␮g/cm2 , respec-
tively) showed an interesting potency, being only twice less active
than indomethacin (Table 2).
Previous experiments showed that, after topical application,
none of the extracts induced skin irritation in the mouse ear at
doses up to 1000 ␮g/cm2 .
432 M. Maldini et al. / Journal of Ethnopharmacology 122 (2009) 430–433

Table 1
Screening of the topical anti-inflammatory of the plants extracts.

Substance No. an. Dose (␮g/cm2 ) Oedema (mg), Mean ± S.E. % Reduction

Controls 10 – 7.3 ± 0.3 –

Acacia cornigera, petroleum ether extract 10 300 4.5 ± 0.2* 38
Acacia cornigera, chloroform extract 10 300 2.1 ± 0.4* 71
Byrsonima crassifolia, petroleum ether extract 10 300 3.1 ± 0.2* 58
Byrsonima crassifolia, chloroform extract 10 300 2.1 ± 0.3* 71
Sphagneticola trilobata, petroleum ether extract 10 300 3.9 ± 0.4* 47
Sphagneticola trilobata, chloroform extract 10 300 2.4 ± 0.3* 67
Sweetia panamensis, petroleum ether extract 10 300 3.5 ± 0.2* 52
Sweetia panamensis, chloroform extract 10 300 2.4 ± 0.3* 67
Indomethacin 10 100 2.9 ± 0.2* 60

Controls 10 – 6.7 ± 0.2 –

Acacia cornigera, methanol extract 10 300 5.6 ± 0.4* 16
Byrsonima crassifolia, methanol extract 10 300 5.4 ± 0.4* 19
Sphagneticola trilobata, methanol extract 10 300 5.9 ± 0.3 12
Sweetia panamensis, methanol extract 10 300 5.5 ± 0.3* 18
*
p < 0.05 at the analysis of variance, as compared with controls.

Table 2
Anti-inflammatory activity of the chloroform extracts.

Substance No. an. Dose (␮g/cm2 ) Oedema (mg), Mean ± S.E. % Reduction ID50 (␮g/cm2 )

Controls 10 – 7.0 ± 0.2 – –

Acacia cornigera 10 30 5.7 ± 0.3* 19 116

10 100 3.4 ± 0.2* 51
10 300 1.9 ± 0.2* 73

Byrsonima crassifolia 10 30 6.2 ± 0.2* 11 112

10 100 3.5 ± 0.3* 50
10 300 1.7 ± 0.2* 76

Sphagneticola trilobata 10 30 6.3 ± 0.3 10 183

10 100 4.7 ± 0.2* 33
10 300 2.6 ± 0.2* 63

Sweetia panamensis 10 30 6.2 ± 0.3 11 180

10 100 4.3 ± 0.3* 39
10 300 2.4 ± 0.3* 66

Indomethacin 10 30 5.9 ± 0.3* 16 93

10 100 2.9 ± 0.3* 59
10 300 1.3 ± 0.2* 81
*
p < 0.05 at the analysis of variance, as compared with controls.

4. Discussion Concerning Acacia cornigera, an in vitro study on the tran-

Preliminary data presented in this study indicate that the
selected medicinal plants have topical anti-inflammatory proper-
ties. In fact, almost all the tested extracts were able to reduce the
Croton oil-induced ear oedema in mice, after topical application.
In particular, the most active extracts were the chloroform ones:
Acacia cornigera and Byrsonima crassifolia barks extracts showed
an activity similar to that the NSAID indomethacin and Sphagneti-
cola trilobata leaves and Sweetia panamensis bark extracts were only
two times less active. Thus, the most suitable solvent to extract the
anti-inflammatory principles from these plants was chloroform,
which suggests their lipophilic properties, and the most promis-
ing extracts were obtained from Byrsonima crassifolia and Acacia
cornigera barks.
Previous studies on Byrsonima crassifolia demonstrated an
antioxidant properties for polar extracts of the bark, leaves and
fruits related to the presence of polyphenol derivatives (Bejar et al.,
1995; Geiss et al., 1995; Rastrelli et al., 1997; Silva et al., 2007; Souza
et al., 2008). Although, polyphenols are known to possess antiphlo-
gistic properties (Biesalski, 2007), other less polar compounds are
likely to be present in the chloroform and petroleum ether extracts,
like as triterpens, sterols and glycolipids (Bejar and Malone, 1993;
Rastrelli et al., 1997) of Byrsonima crassifolia bark, and involved in
their anti-inflammatory effect.
scription factor NF-␬B, involved in inflammation, did not show
any effect for aerial parts (Bork et al., 1996) and no phytochem-
ical investigation are reported, so far. Various species of genus
Acacia are known to contain variety of constituents like leucoan-
thocyanidins, proanthocyanidins, flavonoids, steroids, terpenoids
and alkaloids. Extracts of these species have been reported to pos-
sess insecticidal, molluscicidal, antimicrobial activities (Bimla et al.,
2005).
Phytochemical studies on Sweetia panamensis bark, pyrone
glycosides, (Wiedenfeld and Andrade-Cetto, 2003) and alkaloids
(Fitzgerald et al., 1964; Balandrin and Kinghorn, 1982; Veitch et
al., 1997; Nuzillard et al., 1999) from polar extracts, whereas lupeol
was isolated from hexane extract (Romo et al., 1972). Since lupeol, a
compound of lipophilic nature, is known for its anti-inflammatory
properties also by topical route (Della Loggia et al., 1994; Fernández
et al., 2001), it could be involved in the observed anti-inflammatory
effect of Sweetia panamensis chloroform and/or petroleum ether
extracts.
Studies on polar extracts of Sphagneticola trilobata (syn. Wedelia
trilobata) leaves or aerial parts revealed the presence of different
eudesmanolide sesquiterpenes and kaurane diterpenes (Bohlmann
et al., 1981; Huang et al., 2003; Li et al., 2007; That et al., 2007).
It could be expected their contribution to the anti-inflammatory
effect of the chloroform extract.
 M. Maldini et al. / Journal of Ethnopharmacology 122 (2009) 430–433 433

The obtained results give experimental evidence of a high topical Geiss, F., Heinrich, M., Hunkler, D., Rimpler, H., 1995. Proanthocyanidins with (+)-
anti-inflammatory activity for the lipophilic extracts of four plant epicatechin units from Byrsonima crassifolia bark. Phytochemistry 39, 635–643.
Heinrich, M., Rimpler, H., Barrera, N., 1992. Indigenous phytotherapy of
species traditionally used in Central America for the treatment of gastrointestinal disorders in a lowland Mixe community (Oaxaca, Mex-
inflammatory-based affections. The results also indicate that apolar ico): ethnopharmacologic evaluation. Journal of Ethnopharmacology 36,
solvents would be useful to obtain anti-inflammatory preparations 63–80.
Huang, X.S., Jiang, R.W., Ooi, V., 2003. Trilobolide-6-O-isobutyrate, a eudesmanolide
rather than the traditional aqueous ethnomedicinal remedies. from Wedelia trilobata. Acta Crystallographica E59, 771–772.
Leonti, M., Vibrans, M., Sticher, O., Heinrich, M., 2001. Ethnopharmacology of the
References Popoluca, Mexico: an evaluation. Journal of Pharmacy and Pharmacology 53,
1653–1669.
Li, X., Dong, M., Lin, Y., Shi, Q.-W., Kiyota, H., 2007. Structures and biological properties
Andrade-Cetto, A., Heinrich, M., 2005. Mexican plants with hypoglycaemic effect
of the chemical constituents from the genus Wedelia. Chemistry & Biodiversity
used in the treatment of diabetes. Journal of Ethnopharmacology 99, 325–348.
4, 823–836.
Andrade-Cetto, A., Wiedenfeld, H., 2004. Hypoglycemic effect of Acosmium pana-
Martinez-Vasquez, M., Gonzalez-Esquinica, A.R., Cazares Luna, M., Moreno Gutierrez,
mense bark on streptozotocin diabetic rats. Journal of Ethnopharmacology 90,
M.N., Garcia Argaez, A.N., 1999. Antimicrobial activity of Byrsonima crassifolia (L.)
217–220.
H.B.K. Journal of Ethnopharmacology 66, 79–82.
Arvigo, R., Balik, M., 1993. Rainforest remedies. In: One Hundred Healing Herbs of
Morales, C., Gomez-Serranillos, M.P., Iglesias, I., Villar, A.M., Càceres, A., 2001. Pre-
Belize. Lotus Press, Twin Lakes, WI.
liminary screening of five ethnomedicinal plants of Guatemala. Il Farmaco 56,
Balandrin, M.F., Kinghorn, A.D., 1982. (−)-4␣-Hydroxysparteine, a new natural prod-
523–526.
uct from Acosmium panamense. Heterocycles 19, 1931–1934.
Nuzillard, J.M., Connolly, J.D., Delaude, C., Richard, B., Zeches-Hanrot, M., Le Men-
Bejar, E., Malone, M.H., 1993. Pharmacological and chemical screening of Byrsonima
Olivier, L., 1999. Computer-assisted structural elucidation. Alkaloids with a novel
crassifolia, a medicinal tree from Mexico. Part I. Journal of Ethnopharmacology
diaza-adamantane skeleton from the seeds of Acosmium panamense (Fabaceae).
39, 141–158.
Tetrahedron 55, 11511–11518.
Bejar, E., Amarquaye, A., Che, C., Malone, M., Fong, H., 1995. Constituents of Byrsonima
O’connor, N., Dargan, P.I., Jones, A.L., 2003. Hepatocellular damage from non-
crassifolia and their spasmogenic activity. International Journal of Pharmacog-
steroidal anti-inflammatory drugs. QJM—An International Journal of Medicine
nosy 33, 25–32.
96, 787–791.
Berger, I., Barrientos, A.C., Cáceres, A., Hernández, M., Rastrelli, L., Passreiter, C.M.,
Peraza-Sánchez, S.R., Cen-Pacheco, F., Noh-Chimal, A., May-Pat, F., Simá-Polanco, P.,
Kubelka, W., 1998. Plants used in Guatemala for the treatment of protozoal
Dumonteil, E., García-Miss, M.R., Mut-Martín, M., 2007. Leishmanicidal evalu-
infections. II. Activity of extracts and fractions of five Guatemalan plants against
ation of extracts from native plants of the Yucatan peninsula. Fitoterapia 78,
Trypanosoma cruzi. Journal of Ethnopharmacology 62, 107–115.
315–318.
Biesalski, H.K., 2007. Polyphenols and inflammation: basic interactions. Current
Rastrelli, L., De Tommasi, N., Berger, I., Caceres, A., Saravia, A., De Simone, F., 1997.
Opinion in Clinical Nutrition and Metabolic Care 10, 724–728.
Glycolipids from Byrsonima crassifolia. Phytochemistry 45, 647–650.
Bimla, M., Chander, J., Kalidhar, S.B., 2005. A review on the chemistry and bioactivity
Romo, J., Mundo, H., Carino, M.A., 1972. Isolation and structure of panamine, a com-
of the Acacia spp. Journal of Medicinal and Aromatic Plant Sciences 27, 51–90.
ponent of the Sweetia panamensis. Revista Latinoamericana de Quimica 3, 46–49.
Bohlmann, F., Ziesche, J., King, R.M., Robinson, H., 1981. Eudesmanolides and diter-
Saklatvala, J., 2002. Glucocorticoids: do we know how they work? Arthritis Research
penes from Wedelia trilobata and an ent-kaurenic acid derivative from Aspilia
4, 146–150.
parvifolia. Phytochemistry 20, 751–756.
Schoepe, S., Schäcke, H., May, E., Asadullah, K., 2006. Glucocorticoid therapy-induced
Bork, P.M., Schmitz, M.L., Weimann, C., Kist, M., Heinrich, M., 1996. Nahua Indian
skin atrophy. Experimental Dermatology 15, 406–420.
medicinal plants (Mexico). Inhibitory activity on NF-kB as an anti-inflammatory
Silva, E.M., Souza, J.N.S., Rogez, H., Rees, J.F., Larondelle, Y., 2007. Antioxidant activities
model and antibacterial effects. Phytomedicine 3, 263–269.
and polyphenolic contents of fifteen selected plant species from the Amazonian
Caceres, A., Cano, O., Samoya, B., Aguillar, L., 1990. Plants used in guatemala for
region. Food Chemistry 101, 1012–1018.
the treatment of gastrointestinal disorders. 1. Screening of 84 plants against
Souza, J.N.S., Silva, E.M., Loir, A., Rees, J.-F., Rogez, H., Larondelle, Y., 2008. Antioxi-
enterobacteria. Journal of Ethnopharmacology 30, 55–73.
dant capacity of four polyphenol-rich Amazonian plant extracts: a correlation
Caceres, A., Lopez, B.R., Giron, M.A., Logemann, H., 1991. Plants used in guatemala for
study using chemical and biological in vitro assays. Food Chemistry 106,
the treatment of dermatophytic infections. 1. Screening for antimycotic activity
331–339.
of 44 plant extracts. Journal of Ethnopharmacology 31, 263–276.
Taddei, A., Rosas-Romero, A.J., 1999. Antimicrobial activity of Wedelia trilobata crude
Davies, N.M., Reynolds, J.K., Undeberg, M.R., Gates, B.J., Ohgami, Y., Vega-Villa, K.R.,
extracts. Phytomedicine 6, 133–134.
2006. Minimizing risks of NSAIDs: cardiovascular, gastrointestinal and renal.
That, Q.T., Jossang, J., Jossang, A., Kim, P.P.N., Jaureguiberry, G., 2007. Wedelolides
Expert Review of Neurotherapeutics 6, 1643–1655.
A and B: novel sesquiterpene ␦-lactones, (9R)-Eudesman-9,12-olides, from
Della Loggia, R., Tubaro, A., Sosa, S., Becker, H., Saar, S., Isaac, O., 1994. The role of
Wedelia trilobata. Journal of Organic Chemistry 72, 7102–7105.
triterpenoids in the topical anti-inflammatory activity of Calendula officinalis
Tubaro, A., Dri, P., Del Bello, G., Zilli, C., Della Loggia, R., 1985. The croton oil ear test
flowers. Planta Medica 60, 516–520.
revisited. Agents and Actions 17, 347–349.
Fernández, M.A., de las Heras, B., García, M.D., Sáenz, M.T., Villar, A., 2001. New
Veitch, N.C., Goodwin, B.L., Kite, G.C., Simmonds, M.S.J., 1997. Methoxylated quino-
insights into the mechanism of action of the anti-inflammatory triterpene
lizidine alkaloids from Acosmium panamense. Phytochemistry 45, 847–850.
lupeol. Journal of Pharmacy and Pharmacology 53, 1533–1539.
Wiedenfeld, H., Andrade-Cetto, A., 2003. Pyrone Glycosides from Acosmium pana-
Fitzgerald, T.J., LaPidus, J.B., Beal, J.L., 1964. Sweetinine, an alkaloid from Sweetia
mense (Benth.) Yacovlev. Journal of Biosciences 58, 637–639.
panamensis. Lloydia 27, 107–110.